Process of preparing alkylized purins.



a'rnrur rricn LORENZ ACH, OF MANNI-IEIM, GERMANY, ASSIGNOR TO C. F.BOEllRINGE-R &

SOEIINE, OF MANNHElM-"NALDHOF, GERMANY.

PROCESS OF PREPARiNG ALKYLIZED PURINS.

SPEGIFIGATIQN forming: of Lette s Fatent No, 676,861, dated June 1901-Application filed July 23, 1897- Serial N2, 645,691. ($pcolmcns.)

To a whom it may concern.-

Be it known that I, LORENZ AOH, a citizen of the Empire of Germany,residing at Mannheim, in the Empire of Germany, have invented certainnew and useful Improvements in Preparing Alkylized Purins; and I dohereby declare the following to be a full, clear, and exact descriptionof the invention, such as will enable others skilled in the art to whichIO it appertains to make and use the same.

The present application relates to the art of obtaining derivatives ofthe class of compounds known as purins, and described, for example, inBcrichtc der Deutschen Chem/tschcn GeseZZsc7mf't,Vol. 17, pages 328 and1786, and Abstracts ofthe British Chemical Society, Vol.44, page 996. Itrelates more particularly to the preparation of alkylized halogen purinderivatives, such as the alkylized dichloro- 2o purins,of whichdichlor-oXy-diinethyl-purin having the formula NzCCl 01.0 o--N.on

is an example. (Berichtc, Vol. 17, pages 328 and 1787; Abstracts, Vol.44, page 996.) These bodies have formerly been obtained from variousalkyl derivatives of uric acid and Xanthin, such as theobromin oroaffein,

3 5 by causing phosphorus penta-chlorid in con nection with phosphorusoxy-chlorid acting as a solvent to act upon them. (Bcm'chte dc?Deutschen Ohemt'schen GcseZlschctfl, Vol. 17, page 330, and V0]. 28,page 2480.) These 40 processes, however, involve the use of expensiveraw materials and are hence inapplicable for the production of thesecompounds on a commercial scale.

It is the purpose of this invention to overcome these objections, andwith this purpose in view the same consists in a method which primarilyinvolves the action of haloid ethers upon halogen oXypurins free fromalkyl radicals, which I have been the first to obtain and for which Ihave filed an application for Letters Patent of the United States,executed concurrently herewith and filed June 14, 1897, Serial No.040,762, the said application describing and claiming the same and themethod of their preparation.

My invention also consists in such further steps, methods, and featuresas will be hereinafter set forth and then particularly pointed out inthe claims hereunto annexed.

I have found as the result of my experi- 6o ments and investigationsthat, for example, alkylized dichlor-oxy-purins may readily be obtainedby the reaction which takes place when such alkylizing agentsashalogen-alkyls or other esters suitable for alkylizing purposessnch asalkyl nitrates, alkyl sulfates, di-alkyl sulfates, the alkyl esters ofbenzyl sulfo acids, &c. are brought together with the salts ofdichlor-oxy-purin. For this purpose the dry salts may be taken or theymay be employed in aqueous solution or dissolved in concentrated ordilute alcohol. In all cases the reaction takes place smoothly andwithout difficulty. By the action of one or two molecules of the haloidether upon the acid salt or the neutral salt, respectively, one or bothhydrogen atoms respectively of the imido groups of the dichloroxy-purinare replaced by an alkyl radical. l/Vhen the methyl radical is thusintroduced, we obtain bodies which have already been obtained in otherwaysviz., fl-dichlor-oxymethyl-purin, (E. Fischer in Bemclztc derDctttschcn Chemz'schen Gesellschaft, Vol. 28, page 2490,) ordichlor-oxy-dimethyl-purin, 8 (E. Fischer in Bert'chtc (Zer DetttschcnChem schen Gesellschaft, Vol. 17, page 333.)

The following examples will serve to illustrate my invention in detail,and they embody what I at present consider the best 0 method of carryingout my invention:

1. Alloylie'ing Ct dry saZt-Prcpamtion of dt'methyl chlor 0mg-purin.-Four hundred grains, corresponding to one molecule of the dryneutral lead salt of dichlor-oxy-purin, 5 (PbO N OOl are heated withthree hundred grams (corresponding to two molecules) of methyl iodid andone hundred and fifty cubic centimeters of ether to from to centigradein aclosed vessel and maintained I00 at this temperature for twelvehours. The

resulting mass is boiled out or extracted with alcohol. The dichlor oxydimethylpurin separates out from the concentrated filtrate in needles offine appearance, which melt at 187 centigrade after recrystallizing outof alcohol. The following equation expresses the reaction taking place:

2. Alhylizing in dilute alcohol solwh'on Preparation of mono-methylchlor 000g -pu rin.One kilogram of dichlor-oxy-purin (corresponding toone molecule) is dissolved in Water by the addition of seven hundredgrams (corresponding to two molecules) of caustic potash. The solutionis mixed with equal volume of alcohol and cooled off. Then seven hundredgrams (corresponding to one molecule) of methyl iodid is added, and themixture is allowed to stand for forty-eight hours in a cooling-chamberor refrigerator.

The reaction takes place according to the following equation:

K C N,,OCl |-ICH :K(CH )C N OOl,+ Kl.

The resulting dichlor-oxy-methylpurin is then separated out in finecrystals after evaporating off the alcohol and acidnlating, ac-' cordingto the following equation:

' be greatly varied without departing from my invention.

It is to be observed that my invention under one of its aspects involvesthe action upon a salt of dichlor-oxy-purin with an, alkylizing ester,whether such salt is already formed, as in the first example hereinabovegiven, or is formed duringthe process, as in the second example, and thesecond claim hereunto appended covers both of these methods.

WVhat I claim, therefore, and desire to secure by Letters Patent, is

1. The process which consists in acting upon the salt of adi-haloid-purin with an alkylizing agent.

2. The process which consists in acting upon a salt of dichlor-oxy-purinwith an ester suitable for alkylizing.

3. The process which consists in acting upon the salt of adi-haloid-oxypi1rin with a haloid ether.

4. The process which consists in acting upon a salt of dichlor-oxy-purinwith methyl iodid.

'5. The process which consists in treating dichlor-oxy-purin with analkali and then acting upon the salt so formed with an alkylizing ester.

6. The process which consists in dissolving dichlor-oxy-purin togetherwith an alkali and subsequently treating the solution with an alkylizingester.

7. The process which consists in dissolving dichlor-oxy-purin in water,together with caustic alkali, then adding alcohol and cooling, and thenadding a haloid ether and cooling.

8. The process which consists in dissolving dichlor-oxy-pnrin in watertogether with caustic potash, then adding alcohol and cooling, thentreating with methyl iodid, and finally cooling.

9. The process, which consists in dissolving dichloroxy-purin in Water,together with caustic potash, then adding alcohol and cooling, thentreating with methyl iodid and cooling, and finally separating theresulting dichlor-oxy-methyl-pnrin by evaporating the alcohol.

In testimony whereof I affix my signature in presence of two witnesses.

. LORENZ AOl-I.

\Vitnesses:

FR. AOH, J ACOB ADRIAN.

